HLAB遺傳標記PPT課件

1、 別嘌呤醇作用用途：治療痛風、高尿酸血癥等相關疾病。機理：抑制黃嘌呤氧化酶的活性副作用：皮膚不良反應如HSS、SJS和TEN第1頁/共15頁Patients and Control Subjects Recruitment 228 control individuals： (135 allopurinol-tolerant subjects 93 healthy subjects） 51 patients with allopurinolSCAR第2頁/共15頁SNP Genotyping A total of 823 SNPs： 197 SNPs from 4Mb of the MHC re

2、gion 626 SNPs selected from genes encoding immune-related molecules and drug metabolizing enzymes第3頁/共15頁HLA Genotyping HLA alleles A, B, C, and DRB1, were determined by sequence-specific oligonucleotide reverse lineblot Potential ambiguities were resolved by sequencing-based typing第4頁/共15頁Statistic

3、al Analysis Categorical data were compared between groups with use of Fishers exact tests, and continuous data(presented as median, with range given in parentheses) were compared with use of t tests. All P values were two-tailed; a P value of 0.05 was considered to indicate statistical significance.

4、 Allelic association screen was carried out by the Cochran Armitage Trend test for each SNP . Odds ratios were calculated with Haldanes modification, which adds 0.5 to all cells to accommodate possible zero counts . The corrected P (Pc) values were adjusted by using Bonferronis correction for multip

5、le comparisons to account for the observed alleles (17 for HLA-A, 40 for HLA-B, 19 for HLA-C, and 30 for HLA-DRB1). Therefore, the Pc values were multiplied by a factor of 387,600.第5頁/共15頁Characteristics of Patients and Controls第6頁/共15頁第7頁/共15頁 SJS (13 cases), SJSTEN (5 cases), TEN (3 cases), and HS

6、S (30 cases),第8頁/共15頁第9頁/共15頁Association Screen for Candidate Gene SNPsFig. 1. Screening of candidate SNPs for association with allopurinol-induced SCAR. On the x axis, 823 SNPs are ordered by their chromosome positions; 197 SNPs in the MHC region are those numbered from 260 to 456. On the y axis, t

7、he log10 P values were calculated by comparison of the genotype frequencies between the allopurinolSCAR patients and tolerant group.第10頁/共15頁HLA Allele Frequency第11頁/共15頁Discussion In fact, the association is 100% in that the HLA-B allele B*5801 was present in all 51 patients with allopurinol-induce

8、d SCAR, with an odds ratio exceeding that reported for the association between HLAB27 and ankylosing spondylitis genotyping the B*5801 allele may provide a better guidance of avoiding allopurinol-induced SCAR in patients with renal insufficiency than dosage adjusting. This study, together with the previous reports, suggests that HLA-B alleles andor other genetic polymorphisms in the MHC region might play a major role in the pathogenesis of immune-mediatedSCAR.第12頁/共15頁 HLA-B*5801 is necessary but not sufficient for allopurinolSCAR. The